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| 2. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 4. |
- Zuntini, Alexandre R., et al.
(författare)
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Phylogenomics and the rise of the angiosperms
- 2024
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Ingår i: NATURE. - 0028-0836 .- 1476-4687. ; 629, s. 843-850
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Tidskriftsartikel (refereegranskat)abstract
- Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods(1,2). A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome(3,4). Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins(5-7). However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes(8). This 15-fold increase in genus-level sampling relative to comparable nuclear studies(9) provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.
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| 5. |
- Perez-Escobar, O. A., et al.
(författare)
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Molecular Clocks and Archeogenomics of a Late Period Egyptian Date Palm Leaf Reveal Introgression from Wild Relatives and Add Timestamps on the Domestication
- 2021
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Ingår i: Molecular Biology and Evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 38:10, s. 4475-4492
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Tidskriftsartikel (refereegranskat)abstract
- The date palm, Phoenix dactylifera, has been a cornerstone of Middle Eastern and North African agriculture for millennia. It was first domesticated in the Persian Gulf, and its evolution appears to have been influenced by gene flow from two wild relatives, P. theophrasti, currently restricted to Crete and Turkey, and P. sylvestris, widespread from Bangladesh to the West Himalayas. Genomes of ancient date palm seeds show that gene flow from P. theophrasti to P. dactylifera may have occurred by similar to 2,200years ago, but traces of P. sylvestris could not be detected. We here integrate archeogenomics of a similar to 2,100-year-old P. dactylifera leaf from Saqqara (Egypt), molecular-clock dating, and coalescence approaches with population genomic tests, to probe the hybridization between the date palm and its two closest relatives and provide minimum and maximum timestamps for its reticulated evolution. The Saqqara date palm shares a close genetic affinity with North African date palm populations, and we find clear genomic admixture from both P. theophrasti, and P. sylvestris, indicating that both had contributed to the date palm genome by 2,100years ago. Molecular-clocks placed the divergence of P. theophrasti from P. dactylifera/P. sylvestris and that of P. dactylifera from P. sylvestris in the Upper Miocene, but strongly supported, conflicting topologies point to older gene flow between P. theophrasti and P. dactylifera, and P. sylvestris and P. dactylifera. Our work highlights the ancient hybrid origin of the date palms, and prompts the investigation of the functional significance of genetic material introgressed from both close relatives, which in turn could prove useful for modern date palm breeding.
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| 6. |
- Bowen, C. D., et al.
(författare)
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Comparison of Herpes Simplex Virus 1 Strains Circulating in Finland Demonstrates the Uncoupling of Whole-Genome Relatedness and Phenotypic Outcomes of Viral Infection
- 2019
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 93:8
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Tidskriftsartikel (refereegranskat)abstract
- A majority of adults in Finland are seropositive carriers of herpes simplex viruses (HSV). Infection occurs at epithelial or mucosal surfaces, after which virions enter innervating nerve endings, eventually establishing lifelong infection in neurons of the sensory or autonomic nervous system. Recent data have highlighted the genetic diversity of HSV-1 strains and demonstrated apparent geographic patterns in strain similarity. Though multiple HSV-1 genomes have been sequenced from Europe to date, there is a lack of sequenced genomes from the Nordic countries. Finland's history includes at least two major waves of human migration, suggesting the potential for diverse viruses to persist in the population. Here, we used HSV-1 clinical isolates from Finland to test the relationship between viral phylogeny, genetic variation, and phenotypic characteristics. We found that Finnish HSV-1 isolates separated into two distinct phylogenetic groups, potentially reflecting historical waves of human (and viral) migration into Finland. Each HSV-1 isolate harbored a distinct set of phenotypes in cell culture, including differences in the amount of virus production, extracellular virus release, and cell-type-specific fitness. Importantly, the phylogenetic clusters were not predictive of any detectable pattern in phenotypic differences, demonstrating that whole-genome relatedness is not a proxy for overall viral phenotype. Instead, we highlight specific gene-level differences that may contribute to observed phenotypic differences, and we note that strains from different phylogenetic groups can contain the same genetic variations. IMPORTANCE Herpes simplex viruses (HSV) infect a majority of adults. Recent data have highlighted the genetic diversity of HSV-1 strains and demonstrated apparent genomic relatedness between strains from the same geographic regions. We used HSV-1 clinical isolates from Finland to test the relationship between viral genomic and geographic relationships, differences in specific genes, and characteristics of viral infection. We found that viral isolates from Finland separated into two distinct groups of genomic and geographic relatedness, potentially reflecting historical patterns of human and viral migration into Finland. These Finnish HSV-1 isolates had distinct infection characteristics in multiple cell types tested, which were specific to each isolate and did not group according to genomic and geographic relatedness. This demonstrates that HSV-1 strain differences in specific characteristics of infection are set by a combination of host cell type and specific viral gene-level differences.
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| 7. |
- Conzelmann, A., et al.
(författare)
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Internet-based psychotherapy in children with obsessive-compulsive disorder (OCD): protocol of a randomized controlled trial
- 2022
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obsessive-compulsive disorder (OCD) in children can lead to a huge burden on the concerned patients and their family members. While successful state-of-the art cognitive behavioral interventions exist, there is still a lack of available experts for treatment at home, where most symptoms manifest. Internet-based cognitive behavioral therapy (iCBT) could overcome these restrictions; however, studies about iCBT in children with OCD are rare and mostly target computerized self-help resources and only email contact with the therapist. Therefore, we intended to build up and to evaluate an iCBT approach for children with OCD, replacing successful elements of traditional in-office face-to-face CBT, with face-to-face teleconferences, online materials, and apps. Methods: With the help of a pilot feasibility study, we developed the iCBT consisting of 14 teleconference sessions with the child and parents. The sessions are supported by an app assessing daily and weekly symptoms and treatment course completed by children and parents. Additionally, we obtain heart rate and activity scores from the child via wristbands during several days and exposure sessions. Using a waiting list randomized control trial design, we aim to treat and analyze 20 children with OCD immediately after a diagnostic session whereas the control group of another set of 20 OCD patients will be treated after waiting period of 16 weeks. We will recruit 30 patients in each group to take account for potential dropouts. Outcomes for the treatment group are evaluated before randomization (baseline, t0), 16 weeks (end of treatment, t1), 32 weeks (follow-up 1, t2), and 48 weeks after randomization (follow-up 2, t3). For the waiting list group, outcomes are measured before the first randomization (baseline), at 16 weeks (waiting list period), 32 weeks (end of treatment), 48 weeks after the first randomization (follow-up I), and 64 weeks after the first randomization (follow-up II). Discussion: Based on our experience of feasibility during the pilot study, we were able to develop the iCBT approach and the current study will investigate treatment effectiveness. Building up an iCBT approach, resembling traditional in-office face-to-face therapy, may ensure the achievement of well-known therapy effect factors, the acceptance in both patients and clinicians, and the wide distribution within the health system.
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| 8. |
- Hollmann, K., et al.
(författare)
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Internet-based cognitive behavioral therapy in children and adolescents with obsessive compulsive disorder: a feasibility study
- 2021
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Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 128, s. 1445-1459
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive behavioral therapy (CBT) is the first choice of treatment of obsessive-compulsive disorder (OCD) in children and adolescents. However, there is often a lack of access to appropriate treatment close to the home of the patients. An internet-based CBT via videoconferencing could facilitate access to state-of-the-art treatment even in remote areas. The aim of this study was to investigate feasibility and acceptability of this telemedical approach. A total of nine children received 14 sessions of CBT. The first session took place face-to-face, the remaining 13 sessions via videoconference. OCD symptoms were recorded with a smartphone app and therapy materials were made accessible in a data cloud. We assessed diagnostic data before and after treatment and obtained measures to feasibility, treatment satisfaction and acceptability. Outcomes showed high acceptance and satisfaction on the part of patients with online treatment (89%) and that face-to-face therapy was not preferred over an internet-based approach (67%). The majority of patients and their parents classified the quality of treatment as high. They emphasized the usefulness of exposures with response prevention (E/RP) in triggering situations at home. The app itself was rated as easy to operate and useful. In addition to feasibility, a significant decrease in obsessive-compulsive symptoms was also achieved. Internet-based CBT for pediatric OCD is feasible and well received by the patients and their parents. Furthermore, obsessive-compulsive symptomatology decreased in all patients. The results of this study are encouraging and suggest the significance of further research regarding this technology-supported approach, with a specific focus on efficacy. Trial registration number: Clinical trials AZ53-5400.1-004/44.
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| 9. |
- Isfort, I., et al.
(författare)
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Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Tumors of soft tissue and bone represent a heterogeneous group of neoplasias characterized by a wide variety of genetic aberrations. Albeit knowledge on tumorigenesis in mesenchymal tumors is continuously increasing, specific insights on altered signaling pathways as a basis for molecularly targeted therapeutic strategies are still sparse. The aim of this study was to determine the involvement ofYAP1/TAZ-mediated signals in tumors of soft tissue and bone. Expression levels of YAP1 and TAZ were analyzed by immunohistochemistry in a large cohort of 486 tumor specimens, comprising angiosarcomas (AS), Ewing sarcomas, leiomyosarcomas, malignant peripheral nerve sheath tumors (MPNST), solitary fibrous tumors, synovial sarcomas (SySa), well-differentiated/dedifferentiated/ pleomorphic and myxoid liposarcomas (MLS). Moderate to strong nuclear staining ofYAP1 and TAZ was detected in 53% and 33%, respectively. YAP1 nuclear expression was most prevalent in MPNST, SySa and MLS, whereas nuclear TAZ was predominately detected in AS, MLS and MPNST. In a set of sarcoma cell lines, immunoblotting confirmed nuclear localization ofYAP1 and TAZ, corresponding to their transcriptionally active pool. Suppression ofYAP1/TAZ-TEAD mediated transcriptional activity significantly impaired sarcoma cell viability in vitro and in vivo. Our findings identify nuclear YAP1 and TAZ positivity as a common feature in subsets of sarcomas of soft tissue and bone and provide evidence ofYAP1/TAZ-TEAD signaling as a specific liability to be considered as a new target for therapeutic intervention. Nuclear YAP1/TAZ expression may represent a biomarker suited to identify patients that could benefit fromYAP1/TAZ-TEAD directed therapeutic approaches within future clinical trials.
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| 10. |
- Wilhelmsson, Ulrika, 1970, et al.
(författare)
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Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration
- 2004
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Ingår i: J Neurosci. - 1529-2401. ; 24:21, s. 5016-21
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Tidskriftsartikel (refereegranskat)abstract
- The regenerative capacity of the CNS is extremely limited. The reason for this is unclear, but glial cell involvement has been suspected, and oligodendrocytes have been implicated as inhibitors of neuroregeneration (Chen et al., 2000, GrandPre et al., 2000; Fournier et al., 2001). The role of astrocytes in this process was proposed but remains incompletely understood (Silver and Miller, 2004). Astrocyte activation (reactive gliosis) accompanies neurotrauma, stroke, neurodegenerative diseases, or tumors. Two prominent hallmarks of reactive gliosis are hypertrophy of astrocytic processes and upregulation of intermediate filaments. Using the entorhinal cortex lesion model in mice, we found that reactive astrocytes devoid of the intermediate filament proteins glial fibrillary acidic protein and vimentin (GFAP-/-Vim-/-), and consequently lacking intermediate filaments (Colucci-Guyon et al., 1994; Pekny et al., 1995; Eliasson et al., 1999), showed only a limited hypertrophy of cell processes. Instead, many processes were shorter and not straight, albeit the volume of neuropil reached by a single astrocyte was the same as in wild-type mice. This was accompanied by remarkable synaptic regeneration in the hippocampus. On a molecular level, GFAP-/-Vim-/- reactive astrocytes could not upregulate endothelin B receptors, suggesting that the upregulation is intermediate filament dependent. These findings show a novel role for intermediate filaments in astrocytes and implicate reactive astrocytes as potent inhibitors of neuroregeneration.
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